1. Field of the Invention
The invention relates to naphthalene derivatives which are useful in the treatment of certain dermatological conditions and inhibiting lipoxygenase activity, particularly 5-lipoxygenase activity which makes the compounds useful for topical treatment of inflammatory states. This invention also relates to pharmaceutical compositions useful in relieving the effects of certain chronic recurrent papulosquamous dermatoses, e.g., psoriasis. This invention also relates to a process for preparing compounds of this invention.
2. Related Disclosures
Psoriasis is a skin disease characterized in part by excessive proliferation of cells of the epidermis which remain strongly adherent and build up into a scaley plaque typical of the disease. While currently available therapies, such as corticosteroids, vitamin A derivatives (retinoids), cancer chemotherapeutic agents (methotrexate, razonxane), coal tar and anthralin preparations, and psoralen-u.v. irradiation (PUVA) are effective in controlling the disease to a certain extent, they can cause numerous and sometimes severe undesirable side effects including renal irritation, hepatic toxicity, and erythema.
The compounds 1-hydroxy-2,4-dimethoxynaphthalene, 1-acetoxy-2,4-dimethoxynaphthalene, 1-hydroxy-2,4-diethoxynaphthalene, 1-acetoxy-2,4-diethoxynaphthalene and 1,2-dimethoxy-4-hydroxynaphthalene are known, but no useful biological activity has been ascribed to them. For example, see J. Org. Chem., 34, 2788-90 (1969), J. Org. Chem., 45, 3422-33 (1980) and Liebigs Ann, Chem., 1983, 1886-1900. Certain naphthoquinone derivatives are known to be useful in treating psoriasis. See, for example, U.S. Pat. Nos. 4,229,478, 4,466,981 and 4,593,120 and British Patent No. 1,243,401. Surprisingly, it has been discovered that the compounds of the instant invention area also effective antipsoriatic agents. Compounds of formula (Ic) and (Id), infra, provide prolonged activity in the treatment of psoriasis because of their stability upon application and slow conversion to compounds of formula (Ie) and (If). Further, the compounds of the present invention are more stable in the topical formulations normally used.